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1.
Heliyon ; 10(19): e38491, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39430506

RESUMEN

The complexity of post-fracturing fractures in tight reservoirs is critical for evaluating fracturing effectiveness and is also a significant factor influencing well productivity. Currently, some scholars have utilized an improved G function to study the complexity of hydraulic fractures after fracturing. However, in certain specific construction curves, the characteristics and values of the G function alone are insufficient for comprehensive interpretation. To conduct a more thorough analysis of fracture complexity, this study introduces net pressure and liquid efficiency-parameters related to fracture complexity-based on the G function, and performs statistical analysis. Since the G function curve morphology is image data, it is not suitable for quantitative analysis. Therefore, digital calibration was conducted based on its corresponding morphological features to render it amenable to data analysis. Using Principal Component Analysis (PCA), a comprehensive fracture complexity coefficient was proposed, which considers four parameters: the digital calibration of the G function curve, G function characteristic values, net pressure, and liquid efficiency. The relationship between this coefficient and productivity was examined through Pearson and Spearman correlation analyses, utilizing post-fracturing production data from 26 wells in the Dabei block for validation. The results indicate a significant positive correlation between the comprehensive fracture complexity coefficient and productivity, with a high degree of correlation. This method not only addresses the shortcomings in interpreting certain specific construction curves but also provides a more comprehensive quantitative characterization of fracture complexity. Preliminary validation confirms the applicability of the method, offering valuable insights for evaluating post-fracturing effectiveness.

2.
Cell Death Dis ; 15(8): 586, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39138191

RESUMEN

Anaplastic thyroid cancer (ATC) is among the most aggressive and metastatic malignancies, often resulting in fatal outcomes due to the lack of effective treatments. Prosapogenin A (PA), a bioactive compound prevalent in traditional Chinese herbs, has shown potential as an antineoplastic agent against various human tumors. However, its effects on ATC and the underlying mechanism remain unclear. Here, we demonstrate that PA exhibits significant anti-ATC activity both in vitro and in vivo by inducing GSDME-dependent pyroptosis in ATC cells. Mechanistically, PA promotes lysosomal membrane permeabilization (LMP), leading to the release of cathepsins that activate caspase 8/3 to cleave GSDME. Remarkably, PA significantly upregulates three key functional subunits of V-ATPase-ATP6V1A, ATP6V1B2, and ATP6V0C-resulting in lysosomal over-acidification. This over-acidification exacerbates LMP and subsequent lysosomal damage. Neutralization of lysosomal lumen acidification or inhibition/knockdown of these V-ATPase subunits attenuates PA-induced lysosomal damage, pyroptosis and growth inhibition of ATC cells, highlighting the critical role for lysosomal acidification and LMP in PA's anticancer effects. In summary, our findings uncover a novel link between PA and lysosomal damage-dependent pyroptosis in cancer cells. PA may act as a V-ATPase agonist targeting lysosomal acidification, presenting a new potential therapeutic option for ATC treatment.


Asunto(s)
Lisosomas , Piroptosis , Carcinoma Anaplásico de Tiroides , ATPasas de Translocación de Protón Vacuolares , Lisosomas/metabolismo , Lisosomas/efectos de los fármacos , Humanos , Piroptosis/efectos de los fármacos , ATPasas de Translocación de Protón Vacuolares/metabolismo , Carcinoma Anaplásico de Tiroides/metabolismo , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Animales , Línea Celular Tumoral , Sapogeninas/farmacología , Ratones , Ratones Desnudos , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/tratamiento farmacológico , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Endogámicos BALB C , Gasderminas
3.
J Cereb Blood Flow Metab ; : 271678X241274681, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39161254

RESUMEN

Peroxisome proliferator-activated receptor-γ (PPARγ) plays a protective role against brain injury after stroke in mice. However, the relationship between PPARγ gene polymorphisms and the functional outcome of acute ischemic stroke (AIS) remains unknown. 8822 patients from The Third China National Stroke Registry (CNSR-III) after whole-genome sequencing, two functional single nucleotide polymorphisms(SNPs) in PPARγ, rs1801282 C > G and rs3856806 C > T, were further analysed. The primary outcome was neurological functional disability at three months. Of the 8822 patients, 968 (11.0%) and 3497 (39.6%) were carriers of rs1801282 and rs3856806, respectively. Carriers of rs3856806 showed reduced risks for three-month neurological functional disability (OR, 0.84; 95% CI, 0.73-0.98; p = 0.02) and reduced risks for higher infarct volume (OR 0.90, 95% CI, 0.81-0.99, p = 0.04). They also had a reduced risk of neurological functional disability only in case of lower baseline IL-6 levels (OR 0.64, 95% CI 0.48-0.84, Pinteraction = 0.01). Carriers of rs1801282 had a reduced risk for three-month neurological functional disability (OR 0.77, 95% CI, 0.61-0.99, p = 0.04). Our study suggested that PPARγ polymorphisms are associated with a reduced risk for neurological functional disability and higher infarct volume in AIS. Therefore, PPARγ can be a potential therapeutic target in AIS.

4.
Neurochem Res ; 49(10): 2682-2698, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39002091

RESUMEN

Alzheimer's disease (AD) represents the most widespread neurodegenerative disorder, distinguished by a gradual onset and slow progression, presenting a substantial challenge to global public health. The mitochondrial-associated membrane (MAMs) functions as a crucial center for signal transduction and material transport between mitochondria and the endoplasmic reticulum, playing a pivotal role in various pathological mechanisms of AD. The dysregulation of mitochondrial quality control systems is considered a fundamental factor in the development of AD, leading to mitochondrial dysfunction and subsequent neurodegenerative events. Recent studies have emphasized the role of MAMs in regulating mitochondrial quality control. This review will delve into the molecular mechanisms underlying the imbalance in mitochondrial quality control in AD and provide a comprehensive overview of the role of MAMs in regulating mitochondrial quality control.


Asunto(s)
Enfermedad de Alzheimer , Mitocondrias , Membranas Mitocondriales , Enfermedad de Alzheimer/metabolismo , Humanos , Mitocondrias/metabolismo , Animales , Membranas Mitocondriales/metabolismo , Retículo Endoplásmico/metabolismo
5.
J Am Heart Assoc ; 13(12): e033616, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38874064

RESUMEN

BACKGROUND: We aim to identify the distinct lesion patterns and regions associated with functional outcome and inflammation in patients with acute ischemic stroke, and investigate whether the association between lesion patterns and functional outcome was mediated by inflammation. METHODS AND RESULTS: We performed nonnegative matrix factorization to derived low-dimensional lesion patterns (atoms), and Bayesian linear regression models were applied to explore the associations of lesion patterns with inflammatory factors including high-sensitivity C-reactive protein and interleukin-6, as well as functional outcome (defined as modified Rankin Scale score at 3 months). The difference distribution mean and 95% highest probability density interval (HPDI) were calculated. Mediation analysis was used to examine the mediating effects of inflammation on the relationships between lesion patterns and functional outcome. Seven lesion patterns were derived from 5914 patients with acute ischemic stroke. Lesion patterns distributed in the cortical regions were associated with inflammatory response, including atom 1 (interleukin-6: mean, 0.113 [95% HPDI, 0.073-0.162]; high-sensitivity C-reactive protein: mean, 0.082 [95% HPDI, 0.038-0.123]) and atom 4 (interleukin-6: mean, 0.113 [95% HPDI, 0.071-0.167]; high-sensitivity C-reactive protein: mean, 0.108 [95% HPDI, 0.058-0.165]). These lesion patterns were also significantly associated with functional outcome (atom 1: mean, 1.958 [95% HPDI, 1.538-2.383]; atom 4: mean, 2.245 [95% HPDI, 1.773-2.741]). Mediation analysis suggested that interleukin-6 explained 15.34% and 7.47% in the association of atom 1 and atom 4 with functional outcome, respectively. CONCLUSIONS: Certain lesion patterns that are associated with both inflammation and functional outcome of acute ischemic stroke, especially cortical infarction, may play a role in functional outcome through modulating inflammatory reactions.


Asunto(s)
Proteína C-Reactiva , Inflamación , Interleucina-6 , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Pronóstico , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Persona de Mediana Edad , Interleucina-6/sangre , Biomarcadores/sangre , Teorema de Bayes , Imagen por Resonancia Magnética , Infarto Cerebral/patología
6.
FASEB J ; 38(13): e23751, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38923701

RESUMEN

Mesenchymal stem cells (MSCs) reveal multifaceted immunoregulatory properties, which can be applied for diverse refractory and recurrent disease treatment including acute graft-versus-host disease (aGVHD). Distinguishing from MSCs with considerable challenges before clinical application, MSCs-derived exosomes (MSC-Exos) are cell-free microvesicles with therapeutic ingredients and serve as advantageous alternatives for ameliorating the outcomes of aGVHD. MSC-Exos were enriched and identified by western blotting analysis, NanoSight, and transmission electron microscopy (TEM). Bone marrow-derived MSCs (denoted as MSCs) and exosomes (denoted as MSC-Exos) were infused into the aGVHD SD-Wister rat model via tail vein, and variations in general growth and survival of rats were observed. The level of inflammatory factors in serum was quantized by enzyme-linked immunosorbent assay (ELISA). The pathological conditions of the liver and intestine of rats were observed by frozen sectioning. The ratios of CD4+/CD8+ and Treg cell proportions in peripheral blood, together with the autophagy in the spleen and thymus, were analyzed by flow cytometry. After treatment with MSC-Exos, the survival time of aGVHD rats was prolonged, the clinical manifestations of aGVHD in rats were improved, whereas the pathological damage of aGVHD in the liver and intestine was reduced. According to ELISA, we found that MSC-Exos revealed ameliorative effect upon aGVHD inflammation (e.g., TNF-α, IL-2, INF-γ, IL-4, and TGF-ß) compared to the MSC group. After MSC-Exo treatment, the ratio of Treg cells in peripheral blood was increased, whereas the ratio of CD4+/CD8+ in peripheral blood and the autophagy in the spleen and thymus was decreased. MSC-Exos effectively suppressed the activation of immune cells and the manifestation of the inflammatory response in the aGVHD rat model. Our data would supply new references for MSC-Exo-based "cell-free" biotherapy for aGVHD in future.


Asunto(s)
Exosomas , Enfermedad Injerto contra Huésped , Células Madre Mesenquimatosas , Animales , Exosomas/metabolismo , Enfermedad Injerto contra Huésped/terapia , Ratas , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratas Wistar , Masculino , Ratas Sprague-Dawley , Trasplante de Células Madre Mesenquimatosas/métodos , Linfocitos T Reguladores/inmunología , Células de la Médula Ósea/citología , Autofagia
7.
Stroke ; 55(7): 1798-1807, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38836360

RESUMEN

BACKGROUND: Hemodynamic impairment of blood pressure may play a crucial role in determining the mechanisms of stroke in symptomatic intracranial atherosclerotic stenosis). We aimed to elucidate this issue and assess the impacts of modifications to blood pressure on hemodynamic impairment. METHODS: From the Third China National Stroke Registry III, computed fluid dynamics modeling was performed using the Newton-Krylov-Schwarz method in 339 patients with symptomatic intracranial atherosclerotic stenosis during 2015 to 2018. The major exposures were translesional systolic blood pressure (SBP) drop and poststenotic mean arterial pressure (MAP), and the major study outcomes were cortex-involved infarcts and borderzone-involved infarcts, respectively. Multivariate logistic regression models and the bootstrap resampling method were utilized, adjusting for demographics and medical histories. RESULTS: In all, 184 (54.3%) cortex-involved infarcts and 70 (20.6%) borderzone-involved infarcts were identified. In multivariate logistic model, the upper quartile of SBP drop correlated with increased cortex-involved infarcts (odds ratio, 1.92 [95% CI, 1.03-3.57]; bootstrap analysis odds ratio, 2.07 [95% CI, 1.09-3.93]), and the lower quartile of poststenotic MAP may correlate with increased borderzone-involved infarcts (odds ratio, 2.07 [95% CI, 0.95-4.51]; bootstrap analysis odds ratio, 2.38 [95% CI, 1.04-5.45]). Restricted cubic spline analysis revealed a consistent upward trajectory of the relationship between translesional SBP drop and cortex-involved infarcts, while a downward trajectory between poststenotic MAP and borderzone-involved infarcts. SBP drop correlated with poststenotic MAP negatively (rs=-0.765; P<0.001). In generating hemodynamic impairment, simulating blood pressure modifications suggested that ensuring adequate blood pressure to maintain sufficient poststenotic MAP appears preferable to the reverse approach, due to the prolonged plateau period in the association between the translesional SBP drop and cortex-involved infarcts and the relatively short plateau period characterizing the correlation between poststenotic MAP and borderzone-involved infarcts. CONCLUSIONS: This research elucidates the role of hemodynamic impairment of blood pressure in symptomatic intracranial atherosclerotic stenosis-related stroke mechanisms, underscoring the necessity to conduct hemodynamic assessments when managing blood pressure in symptomatic intracranial atherosclerotic stenosis.


Asunto(s)
Presión Sanguínea , Hemodinámica , Arteriosclerosis Intracraneal , Accidente Cerebrovascular , Humanos , Masculino , Arteriosclerosis Intracraneal/fisiopatología , Arteriosclerosis Intracraneal/complicaciones , Femenino , Persona de Mediana Edad , Anciano , Presión Sanguínea/fisiología , Hemodinámica/fisiología , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/epidemiología , Sistema de Registros , Constricción Patológica/fisiopatología , China/epidemiología
8.
Cureus ; 16(4): e57503, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38707011

RESUMEN

BACKGROUND: Life satisfaction is a comprehensive psychological index to measure a person's life quality. Previous studies have found that population sociological factors, physiological factors, psychological factors, and social factors all affect life satisfaction, but few studies have looked at the role of stable psychological factors, such as personality, in life satisfaction. Thus, this study combined previous research results and theories to study the current situation of college students' life satisfaction and its correlation with personality. OBJECTIVE: This study aims to comprehensively assess the life satisfaction levels among university students enrolled in a medical college in China, explore their correlation with various demographic factors and personality traits, identify potential areas for intervention, and provide recommendations for improving students' overall well-being and fostering the development of a positive and healthy personality. METHODS: A stratified cluster sampling method was used to select college students from a university. The questionnaire consists of general characteristics, a life satisfaction scale, and the Big Five Inventory. Descriptive statistical methods were conducted to describe the college students' life satisfaction status; an analysis of variance was performed to compare the score of life satisfaction among different demographic features; and the correlation between the score of life satisfaction and the Big Five Inventory was also analyzed. RESULTS: A total of 3116 subjects were included in this survey. The life satisfaction of females was higher than that of males in the dimensions of family, friends, school, and overall satisfaction (p<0.05). The life satisfaction of males in the self dimension was higher than that of females (p<0.05). The life satisfaction of different weight types had statistical significance in the life dimension (p<0.05). The life satisfaction of family, school, and overall well-being among smoking college students was lower than that of non-smoking college students (p<0.05). The life satisfaction of non-drinking college students in family, friends, life, school, and overall life satisfaction scores was higher than those of drinking college students (p<0.05). College students who get plenty of sleep a day (more than eight hours) scored higher life satisfaction scores in the self dimension than sleep-deprived college students (p<0.05). In addition to the family dimension, students taking long physical exercise breaks every day had higher life satisfaction scores in every dimension than students lacking physical exercise (p<0.05). The mean score of personality in the agreeableness and openness dimensions is the highest. Correlation analysis showed that the personality score in each dimension was positively correlated with the life satisfaction score in each dimension except for the neuroticism dimension of personality (p<0.05). CONCLUSION: The life satisfaction of college students is different for different lifestyles. The student management department should pay attention to the physical and mental health of college students with low life satisfaction and further find out the reasons for the difference in life satisfaction. Meanwhile, education should be strengthened for college students and encourage them to give up smoking and alcohol; strengthen physical training; and university education should strengthen the personality cultivation of college students.

9.
Ecotoxicol Environ Saf ; 277: 116378, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38663191

RESUMEN

Pesticide residues and microplastics (MPs) in agricultural soils are two major concerns for soil health and food safety. The degradation of chlorpyrifos (CPF), an organophosphorus pesticide, releases phosphates. This process may be affected by the presence of MPs in the soil. The combination of CPF and MPs presence in the soil may thus produce interaction effects that alter the soil phosphorus (P) balance. This study explores the degradation pathways of CPF (6 mg kg-1, 12 mg kg-1 of CPF addition) in soils with different levels of polylactic acid MPs (PLA-MPs) (0.0 %, 0.1 %, 0.5 %, 1.0 % w/w), and analyzes soil P fractions and phosphatase enzyme activities to investigate soil P bioavailability under different treatments. Results show that the degradation of CPF fits to a first-order decay model, with half-lives (DT50) ranging from 11.0 to 14.8 d depending on PLA-MPs treatment. The concentration of its metabolite 3, 5, 6-trichloropyridine 2-phenol (TCP) reached a peak of 0.93-1.67 mg kg-1 within 7-14 days. Similarly, the degradation of CPF led to a significant transient increase in P bioavailability within 3-7 days (p < 0.05), with a peak range of 22.55-26.01 mg kg-1 for Olsen-P content and a peak range of 4.63-6.76 % for the proportions of available P fractions (H2O-P+NaHCO3-P+NaOH-P), before returning to prior levels (Olsen-P: 11.28-19.52 mg kg-1; available soil P fractions: 4.15-5.61 %). CPF degradation (6 mg kg-1) was significantly inhibited in soil with 1.0 % PLA-MPs addition. The effects of MPs and CPF on soil P fractions occur at different time frames, implying that their modes of action and interactions with soil microbes differ.


Asunto(s)
Cloropirifos , Microplásticos , Fósforo , Contaminantes del Suelo , Suelo , Contaminantes del Suelo/análisis , Contaminantes del Suelo/metabolismo , Fósforo/análisis , Suelo/química , Disponibilidad Biológica , Biodegradación Ambiental , Poliésteres/química , Poliésteres/metabolismo , Insecticidas/análisis
10.
J Cell Mol Med ; 28(7): e18182, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38498903

RESUMEN

Chromosome instability (CIN) is a common contributor driving the formation and progression of anaplastic thyroid cancer (ATC), but its mechanism remains unclear. The BUB1 mitotic checkpoint serine/threonine kinase (BUB1) is responsible for the alignment of mitotic chromosomes, which has not been thoroughly studied in ATC. Our research demonstrated that BUB1 was remarkably upregulated and closely related to worse progression-free survival. Knockdown of BUB1 attenuated cell viability, invasion, migration and induced cell cycle arrests, whereas overexpression of BUB1 promoted the cell cycle progression of papillary thyroid cancer cells. BUB1 knockdown remarkably repressed tumour growth and tumour formation of nude mice with ATC xenografts and suppressed tumour metastasis in a zebrafish xenograft model. Inhibition of BUB1 by its inhibitor BAY-1816032 also exhibited considerable anti-tumour activity. Further studies showed that enforced expression of BUB1 evoked CIN in ATC cells. BUB1 induced CIN through phosphorylation of KIF14 at serine1292 (Ser1292 ). Overexpression of the KIF14ΔSer1292 mutant was unable to facilitate the aggressiveness of ATC cells when compared with that of the wild type. Collectively, these findings demonstrate that the BUB1/KIF14 complex drives the aggressiveness of ATC by inducing CIN.


Asunto(s)
Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Animales , Ratones , Humanos , Carcinoma Anaplásico de Tiroides/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Ratones Desnudos , Pez Cebra/metabolismo , Inestabilidad Cromosómica , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Línea Celular Tumoral , Proteínas Oncogénicas/genética , Cinesinas/genética
11.
Reprod Biomed Online ; 48(4): 103685, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38324980

RESUMEN

RESEARCH QUESTION: What role does programmed cell death 4 (PDCD4) play in premature ovarian insufficiency (POI)? DESIGN: A PDCD4 gene knockout (PDCD4-/-) mouse model was constructed, a POI mouse model was established similar to human POI with 4-vinylcyclohexene dioxide (VCD), a PDCD4-overexpressed adenovirus was designed and the regulatory role in POI in vitro and in vivo was investigated. RESULTS: PDCD4 expression was significantly increased in the ovarian granulosa cells of patients with POI (P ≤ 0.002 protein and mRNA) and mice with VCD-induced POI (P < 0.001 protein expression in both mouse ovaries and granulosa cells). In POI-induced mice model, PDCD4 knockouts significantly increased anti-Müllerian hormone, oestrodiol and numbers of developing follicles, and the PI3K-AKT-Bcl2/Bax signalling pathway is involved in it. CONCLUSION: The expression and regulation of PDCD4 significantly affects the POI pathology in a mouse model. This effect is closely related to the regulation of Bcl2/Bax and the activation of the PI3K-AKT signalling pathway.


Asunto(s)
Ciclohexenos , Insuficiencia Ovárica Primaria , Animales , Femenino , Humanos , Ratones , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Modelos Animales de Enfermedad , Fosfatidilinositol 3-Quinasas/metabolismo , Insuficiencia Ovárica Primaria/inducido químicamente , Insuficiencia Ovárica Primaria/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas de Unión al ARN/genética
12.
Food Funct ; 15(2): 853-865, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38164977

RESUMEN

The microecological stability of the gut microbiota plays a pivotal role in both preventing and treating colorectal cancer (CRC). This study investigated whether Lactobacillus plantarum CBT (LP-CBT) prevents CRC by inducing alterations in the gut microbiota composition and associated metabolites. The results showed that LP-CBT inhibited colorectal tumorigenesis in azoxymethane/dextran sulfate sodium (AOM/DSS)-treated mice by repairing the intestinal barrier function. Furthermore, LP-CBT decreased pro-inflammatory cytokines and anti-inflammatory cytokines. Importantly, LP-CBT remodeled intestinal homeostasis by increasing probiotics (Coprococcus, Mucispirillum, and Lactobacillus) and reducing harmful bacteria (Dorea, Shigella, Alistipes, Paraprevotella, Bacteroides, Sutterella, Turicibacter, Bifidobacterium, Clostridium, Allobaculum), significantly influencing arginine biosynthesis. Therefore, LP-CBT treatment regulated invertases and metabolites associated with the arginine pathway (carbamoyl phosphate, carboxymethyl proline, L-lysine, 10,11-epoxy-3-geranylgeranylindole, n-(6)-[(indol-3-yl)acetyl]-L-lysine, citrulline, N2-succinyl-L-ornithine, and (5-L-glutamyl)-L-glutamate). Furthermore, the inhibitory effect of LP-CBT on colorectal cancer was further confirmed using the MC38 subcutaneous tumor model. Collectively, these findings offer compelling evidence supporting the potential of LP-CBT as a viable preventive strategy against CRC.


Asunto(s)
Colitis , Neoplasias Colorrectales , Microbioma Gastrointestinal , Lactobacillus plantarum , Animales , Ratones , Lactobacillus plantarum/metabolismo , Lisina/farmacología , Citocinas/metabolismo , Metaboloma , Neoplasias Colorrectales/metabolismo , Arginina/metabolismo , Sulfato de Dextran/farmacología , Modelos Animales de Enfermedad , Colitis/microbiología , Ratones Endogámicos C57BL
13.
Stroke Vasc Neurol ; 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-37699726

RESUMEN

BACKGROUND: Given the swift advancements in artificial intelligence (AI), the utilisation of AI-based clinical decision support systems (AI-CDSSs) has become increasingly prevalent in the medical domain, particularly in the management of cerebrovascular disease. AIMS: To describe the design, rationale and methods of a cluster-randomised multifaceted intervention trial aimed at investigating the effect of cerebrovascular disease AI-CDSS on the clinical outcomes of patients who had a stroke and on stroke care quality. DESIGN: The GOLDEN BRIDGE II trial is a multicentre, open-label, cluster-randomised multifaceted intervention study. A total of 80 hospitals in China were randomly assigned to the AI-CDSS intervention group or the control group. For eligible participants with acute ischaemic stroke in the AI-CDSS intervention group, cerebrovascular disease AI-CDSS will provide AI-assisted imaging analysis, auxiliary stroke aetiology and pathogenesis analysis, and guideline-based treatment recommendations. In the control group, patients will receive the usual care. The primary outcome is the occurrence of new vascular events (composite of ischaemic stroke, haemorrhagic stroke, myocardial infarction or vascular death) at 3 months after stroke onset. The sample size was estimated to be 21 689 with a 26% relative reduction in the incidence of new composite vascular events at 3 months by using multiple quality-improving interventions provided by AI-CDSS. All analyses will be performed according to the intention-to-treat principle and accounted for clustering using generalised estimating equations. CONCLUSIONS: Once the effectiveness is verified, the cerebrovascular disease AI-CDSS could improve stroke care and outcomes in China. TRIAL REGISTRATION NUMBER: NCT04524624.

14.
J Surg Res ; 295: 811-819, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38160492

RESUMEN

INTRODUCTION: Ventilator-induced lung injury (VILI) is the most common complication associated with mechanical ventilation. Electroacupuncture (EA) has shown potent anti-inflammatory effects. This study aimed to investigate the effects of EA on VILI and explore the underlying mechanisms. METHODS: Male C57BL/6 mice were subjected to high tidal volume ventilation to induce VILI. Prior to mechanical ventilation, mice received treatment with EA, nonacupoint EA, or EA combined with zinc protoporphyrin. RESULTS: EA treatment significantly improved oxygenation, as indicated by increased PaO2 levels in VILI mice. Moreover, EA reduced lung injury score, lung wet/dry weight ratio, and protein concentration in bronchoalveolar lavage fluid. EA also decreased the expression of pro-inflammatory cytokines including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, IL-18, chemokine keratinocyte chemoattractant, macrophage inflammatory protein 2, and malondialdehyde. Furthermore, EA increased the activities of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase in VILI mice. At the molecular level, EA upregulated the expression of Nrf2 (nucleus) and heme oxygenase -1, while down-regulating the expression of p-NF-κB p65, NLR Family Pyrin Domain Containing 3, Cleaved Caspase-1, and ASC in VILI mice. Notably, the effects of EA were reversed by zinc protoporphyrin treatment, nonacupoint EA did not affect the aforementioned indicators of VILI. CONCLUSIONS: EA alleviates VILI by inhibiting the NLR Family Pyrin Domain Containing three inflammasome through activation of the Nrf2/HO-1 pathway.


Asunto(s)
Electroacupuntura , Lesión Pulmonar Inducida por Ventilación Mecánica , Ratones , Masculino , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Ratones Endogámicos C57BL , Pulmón/patología , Lesión Pulmonar Inducida por Ventilación Mecánica/prevención & control , Lesión Pulmonar Inducida por Ventilación Mecánica/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR
15.
J Am Heart Assoc ; 12(21): e028569, 2023 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-37889177

RESUMEN

Background White matter hyperintensities (WMHs) are areas of increased signal intensity on T2-weighted magnetic resonance imaging (MRI). WMH penumbra may be a potential target for early intervention in WMHs. We explored the relationship between angiogenesis and WMH penumbra in patients with WMHs. Methods and Results Twenty-one patients with confluent WMHs of Fazekas grade ≥2 were included. All the participants underwent 68Ga-NOTA-PRGD2 positron emission tomography/magnetic resonance imaging. WMH penumbra was analyzed with masks created for the WMH and 7 normal-appearing white matter layers; each layer was dilated away from the WMH by 2 mm. Angiogenesis array and ELISA were used to detect the serum levels of angiogenic factors, inflammatory factors, HIF-1 alpha, and S100B. Fourteen patients with increased 68Ga-NOTA-PRGD2 maximum standardized uptake (>0.17) were classified into group 2. Seven patients with maximum standardized uptake ≤0.17 were classified as group 1. WMH volume and serum levels of integrin αvß3, vascular endothelial growth factor receptor 22, and interleukin-1ß tended to be higher in group 2 than in group 1. In group 2, 68Ga-NOTA-PRGD2 uptake was significantly increased at the border between the WMH and normal-appearing white matter than in WMHs (P=0.004). The structure penumbra, defined by fractional anisotropy, was wider in group 2 (8 mm) than in group 1 (2 mm). The cerebral blood flow penumbra was 12 mm in both groups. Angiogenesis showed a correlation with reduced cerebral blood flow and microstructure integrity. Conclusions Our study provides evidence that angiogenesis occurs in the WMH penumbra. Further studies are warranted to verify the effect of angiogenesis on WMH growth.


Asunto(s)
Sustancia Blanca , Humanos , Sustancia Blanca/patología , Radioisótopos de Galio , Factor A de Crecimiento Endotelial Vascular , Imagen por Resonancia Magnética/métodos
16.
Hum Reprod ; 38(12): 2447-2455, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-37879850

RESUMEN

STUDY QUESTION: Do women have worse pregnancy and neonatal outcomes of IVF/ICSI-fresh embryo transfer (ET) after conservative treatment of atypical hyperplasia (AH)? SUMMARY ANSWER: AH has no impact on live birth but is associated with increased risks of pregnancy loss and preterm delivery (PTD). WHAT IS KNOWN ALREADY: AH is a precancerous lesion of endometrial cancer. Several recognized AH risk factors include nulliparity, increased body mass index, ovulation disorders, diabetes mellitus, and others. As such, patients are suggested to attempt conception upon achieving AH regression. Recently, successful pregnancies with IVF/ICSI have been increasingly reported. STUDY DESIGN, SIZE, DURATION: Forty-two patients with AH regression and 18 700 women with no evidence of endometrial abnormality, who underwent their first autologous oocytes' retrieval and fresh ET cycles of IVF/ICSI in the Center for Reproductive Medicine, Shandong University, from May 2008 to July 2021, were retrospectively enrolled. PARTICIPANTS/MATERIALS, SETTING, METHODS: First, 42 AH patients were propensity score matched with control women (n = 168) at a 1:4 ratio. Reproductive outcomes and maternal/neonatal complications were compared between the matched pairs. Binary logistic regression analyses were conducted to assess odds ratios (ORs) of AH for live birth, pregnancy loss, and PTD from AH women and all 18 700 eligible controls. MAIN RESULT AND THE ROLE OF CHANCE: Patients with AH achieved a numerically lower live birth rate (LBR) as compared to the matched controls, but without significant difference (26% versus 37%, P = 0.192). However, compared with the matched controls, AH patients showed significantly higher rates of pregnancy loss (52% versus 21%, P = 0.003) and PTD (45% versus 16%, P = 0.041). Further analyses revealed a statistically significantly increased rate of late pregnancy loss (17% versus 3%, P = 0.023), but not early miscarriage (35% versus 18%, P = 0.086), in the AH group. Furthermore, after correcting for potential confounders, the likelihood of a live birth in AH patients narrowly failed to be statistically significantly different from controls (adjusted OR [aOR]: 0.51, 95% CI: 0.25-1.04, P = 0.064). Nonetheless, the logistic regression reconfirmed that AH was an independent risk factor for pregnancy loss (aOR: 3.62, 95% CI: 1.55-8.46, P = 0.003), late pregnancy loss (aOR: 9.33, 95% CI: 3.00-29.02, P < 0.001), and PTD (aOR: 5.70, 95% CI: 1.45-22.38, P = 0.013). LIMITATIONS, REASONS FOR CAUTION: Selection bias was an inherent drawback of this study. First, because of the low AH prevalence among women receiving IVF/ICSI treatment, and consequently, limited sample size, the relationship between AH with LBR and adverse complications might be concealed and underestimated. Hence, the results should be interpreted cautiously. Similarly, the impacts of diverse clinical features of AH patients on the pregnancy outcomes need further studies in a larger population. Second, although most data used in this study were obtained by reviewing the medical records, missing data did exist and so did the recall bias. Third, although the propensity score matching and multivariable logistic models were performed collectively in order to minimize potential confounders between AH and controls, the intrinsic disadvantages of the retrospective nature of this study could not be avoided completely, and additional confirmation bias might be induced with reduplication of statistical analyses. WIDER IMPLICATION OF THE FINDINGS: Our results highlight the necessity of adequate counseling and intensive pregnancy monitoring for AH individuals and their families. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the National Key Research & Developmental Program of China (2022YFC2703800), the Natural Science Foundation of Shandong Province (ZR2022MH009), and Projects of Medical and Health Technology Development Program in Shandong Province (202005010520, 202005010523). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.


Asunto(s)
Aborto Espontáneo , Lesiones Precancerosas , Nacimiento Prematuro , Embarazo , Recién Nacido , Humanos , Femenino , Resultado del Embarazo , Estudios Retrospectivos , Fertilización In Vitro , Inyecciones de Esperma Intracitoplasmáticas/métodos , Hiperplasia , Puntaje de Propensión , Tratamiento Conservador , Transferencia de Embrión/métodos , Nacimiento Vivo , Tasa de Natalidad , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Índice de Embarazo
17.
Adv Mater ; 35(45): e2305535, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37607503

RESUMEN

The progress of solar-driven water-splitting technology has been impeded by the limited light response capability of semiconductor materials. Despite attempts to leverage nearly 50% of infrared radiation for photothermal synergy and catalytic reaction enhancement, heat loss during liquid phase reactions results in low energy conversion efficiency. Here, the photothermally driven catalytic water-splitting system, which designs K-SrTiO3 -loaded TiN silica wool at the water-air interface. Photocatalytic tests and density functional theory calculations demonstrate that the thermal effect transforms liquid water into water vapor, thereby reducing the reaction free energy of catalysts and improving the transmission rate of catalytic products. Hence, the hydrogen evolution rate reaches 275.46 mmol m-2  h-1 , and the solar-to-hydrogen (STH) efficiency is 1.81% under 1 sun irradiation in this gas-solid system, which is more than twice that of liquid water splitting. This novel photothermal catalytic pathway, which involves a coupled reaction of water evaporation and water splitting, is anticipated to broaden the utilization range of the solar spectrum and significantly enhance the conversion efficiency of STH.

18.
ACS Nano ; 17(12): 11616-11625, 2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37317581

RESUMEN

Most of the existing photocatalysts can only use ultraviolet light and part of visible light, so broadening the spectrum response range and realizing the full spectrum coverage are key measures to improve the solar-to-hydrogen (STH) efficiency of photocatalytic water splitting. A spatially separated photothermal coupled photocatalytic (PTC) reaction system was designed using carbonized melamine foam (C-MF) as a substrate to absorb visible and infrared light and Cu0.04In0.25ZnSy@Ru (CIZS@Ru) as a photocatalyst to absorb UV-visible light (UV-vis). By comparing the three modes of bottom, liquid level, and self-floating, it is found that the surface temperature of the system has a significant effect on the hydrogen evolution activity. The monochromatic light and activation energy experiments verify that the enhancement of photocatalytic activity comes from the strengthened photothermal effect of the substrate. Combined with theoretical calculations, it is further confirmed that the introduction of photothermal materials provides additional kinetic energy for carrier transmission and promotes directional carrier transmission efficiency. Based on the photoenergy-thermal integrated catalytic strategy, the hydrogen production rate reaches 603 mmol h-1 m-2. The structural design of photocatalysis has potential application in the field of photoenergy-fuel conversion.

19.
Nutrients ; 15(12)2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-37375669

RESUMEN

Maternal folate has been shown to relate to the risk of gestational diabetes mellitus (GDM). However, the existing studies have yielded inconsistent conclusions. The purpose of this study was to systematically review the association between maternal folate status and the risk of GDM. Observational studies up to 31 October 2022 were included. Study characteristics, the means and standard deviations (SDs) of folate levels (serum/red blood cell (RBC)), the odds ratios (ORs) with 95% confidence intervals (CIs) and the time for folate measurement were extracted. Compared with the non-GDM group, serum and RBC folate levels in women with GDM were significantly higher. Our subgroup analysis demonstrated that serum folate levels in the GDM group were significantly higher than in the non-GDM group only in the second trimester. RBC folate levels in the GDM group were significantly higher than in the non-GDM group in the first and second trimesters. Taking serum/RBC folate levels as continuous variables, the adjusted odds ratios of GDM risk showed that increased serum folate concentration rather than RBC folate elevated the risk of GDM. In the descriptive analysis, five studies reported high serum folate levels increased GDM risk, whereas the other five showed no association between serum folate levels and GDM risk. Moreover, the rest three studies pointed out high RBC folate levels increased GDM risk. Altogether we found that the risk of GDM is associated with high serum/plasma and RBC folate levels. Future studies should determine the recommended folic acid cutoff balancing the risk for GDM and fetal malformations.


Asunto(s)
Diabetes Gestacional , Embarazo , Femenino , Humanos , Ácido Fólico
20.
Front Public Health ; 11: 1169128, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37333519

RESUMEN

Purpose: We aim to develop myopia classification models based on machine learning algorithms for each schooling period, and further analyze the similarities and differences in the factors influencing myopia in each school period based on each model. Design: Retrospective cross-sectional study. Participants: We collected visual acuity, behavioral, environmental, and genetic data from 7,472 students in 21 primary and secondary schools (grades 1-12) in Jiamusi, Heilongjiang Province, using visual acuity screening and questionnaires. Methods: Machine learning algorithms were used to construct myopia classification models for students at the whole schooling period, primary school, junior high school, and senior high school period, and to rank the importance of features in each model. Results: The main influencing factors for students differ by school section, The optimal machine learning model for the whole schooling period was Random Forest (AUC = 0.752), with the top three influencing factors being age, myopic grade of the mother, and Whether myopia requires glasses. The optimal model for the primary school period was a Random Forest (AUC = 0.710), with the top three influences being the myopic grade of the mother, age, and extracurricular tutorials weekly. The Junior high school period was an Support Vector Machine (SVM; AUC = 0.672), and the top three influencing factors were gender, extracurricular tutorial subjects weekly, and whether can you do the "three ones" when reading and writing. The senior high school period was an XGboost (AUC = 0.722), and the top three influencing factors were the need for spectacles for myopia, average daily time spent outdoors, and the myopic grade of the mother. Conclusion: Factors such as genetics and eye use behavior all play an essential role in students' myopia, but there are differences between school periods, with those in the lower levels focusing on genetics and those in the higher levels focusing on behavior, but both play an essential role in myopia.


Asunto(s)
Miopía , Femenino , Humanos , Estudios Retrospectivos , Estudios Transversales , Miopía/epidemiología , Estudiantes , Instituciones Académicas , Aprendizaje Automático
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